Erlotinib plus either pazopanib or placebo in patients with previously treated advanced non-small cell lung cancer: A randomized, placebo-controlled phase 2 trial with correlated serum proteomic signatures.

BACKGROUND: This study compared the efficacy and safety of treatment with erlotinib plus pazopanib versus erlotinib plus placebo in patients with previously treated advanced non-small cell lung cancer (NSCLC). METHODS: Patients with progressive-stage IV NSCLC after either 1 or 2 previous chemotherapy regimens were randomized to receive erlotinib (150 mg by mouth daily) with either pazopanib (600 mg by mouth daily) or placebo. During treatment, patients were evaluated every 8 weeks until disease progression or unacceptable toxicity. After a study amendment, pretreatment serum specimens for the VeriStrat assay were collected. The predictive value of the VeriStrat score (good vs poor) for progression-free survival (PFS) and overall survival (OS) was assessed in the overall population and in each treatment group. RESULTS: One hundred ninety-two eligible patients were randomized between February 2010 and February 2011. PFS was prolonged with erlotinib plus pazopanib versus erlotinib plus placebo (median, 2.6 vs 1.8 months; hazard ratio, 0.58; P = .001). There was no difference in the OS of the 2 groups. A good VeriStrat score predicted longer PFS and OS in the entire group and predicted longer PFS in the subgroup receiving erlotinib plus pazopanib. The addition of pazopanib increased toxicity, and this was consistent with the known toxicity profile. CONCLUSIONS: The addition of pazopanib to erlotinib in an unselected group of patients with previously treated NSCLC improved PFS and increased treatment-related toxicity, but it had no influence on OS. The efficacy of both regimens was modest. Patients receiving erlotinib plus pazopanib had longer PFS if they had a good VeriStrat score versus a poor one. Cancer 2018;124:2355-64. © 2018 American Cancer Society.

Amrubicin and carboplatin with pegfilgrastim in patients with extensive stage small cell lung cancer: A phase II trial of the Sarah Cannon Oncology Research Consortium.

PURPOSE: First-line treatment for patients with extensive-stage small cell lung cancer (SCLC) includes treatment with platinum-based combination chemotherapy. Amrubicin is a synthetic anthracycline with single-agent activity in relapsed/refractory SCLC. In an attempt to improve treatment efficacy, we evaluated amrubicin/carboplatin as first-line therapy for extensive-stage SCLC. PATIENTS AND METHODS: In this multicenter phase II trial, patients received amrubicin (30 mg/m2 daily on Days 1, 2, and 3) and carboplatin (AUC = 5 on Day 1); cycles were repeated every 21 days for 4 cycles. Pegfilgrastim (6 mg subcutaneously) was administered on Day 4 of all cycles. Overall survival (OS) proportion at 1 year was the primary endpoint. The target 1-year OS rate was 47%, an improvement of 35% from historical results with carboplatin/etoposide. RESULTS: Eighty patients received study treatment, and 62% completed the planned 4 courses. The overall response rate was 74% (13% complete responses). The 1-year survival rate was 38% (95% CI: 25, 50). The median survival was 10 months. Myelosuppression was severe but manageable. CONCLUSIONS: The combination of amrubicin/carboplatin was an active first-line treatment for extensive stage SCLC, but showed no indication of increased efficacy compared to standard treatments. Severe myelosuppression was common with this regimen, in spite of prophylactic pegfilgrastim. These results are consistent with those of other trials in showing no role for amrubicin in the first-line treatment of SCLC.

Paclitaxel/carboplatin/etoposide versus paclitaxel/topotecan for extensive-stage small cell lung cancer: a Minnie Pearl Cancer Research Network randomized, prospective phase II trial.

PURPOSE: To compare the combination of paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and topotecan (Hycamtin; Glaxo SmithKline, Philadelphia, http://www.gsk.com) with paclitaxel, carboplatin (Paraplatin; Bristol-Myers Squibb), and etoposide (Etopophos, VePesid; Bristol-Myers Squibb) in patients with previously untreated extensive-stage small cell lung cancer. PATIENTS AND METHODS: In this phase II trial, 120 patients were randomly allocated to receive either topotecan (1.5 mg/m(2) i.v. days 1, 2, and 3) and paclitaxel (175 mg/m(2) i.v. day 1) every 21 days orpaclitaxe l (200 mg/m(2) i.v. day 1), carboplatin (area under the concentration-time curve 6 i.v. day 1), and etoposide (50 mg/100 mg alternating daily by mouth days 1-10) every 21 days, each regimen for a maximum of eight cycles. The primary end points were objective response rate and time to progression. RESULTS: The paclitaxel-carboplatin-etoposide combination produced a significantly higher overall response rate (78% versus 48%), longer median time to progression (7.6 months versus 5.5 months), and greater number of patients free from progression at 1 year (14% versus 8%) compared with paclitaxel plus topotecan. There was no difference in overall survival. Toxicities were similar in the two treatment arms. CONCLUSIONS: The paclitaxel-carboplatin-etoposide combination produced a superior overall response rate and time to progression in patients with extensive-stage small cell lung cancer compared with paclitaxel plus topotecan. The platinum compounds continue to be a necessary component of the initial therapy for these patients.